Quinidine gluconate sustained medication tablet



Patented July 2145959 United States Patent ce EXAMPLE 1 v 2,895,881 This example represents a 10 grain tablet containing 5 grains of quinidine gluconate and is made'from a two part granulation, as follows:

Part A 2 grainsquinidine gluconate QUINIDINE GLUCONATE SUSTAINED IVIEDICATION TABLET Tsugio Hamada, Philadelphia, Pa., assignor to Wynn Pharmacal Corporation, Philadelphia, Pa., a corporationof Pennsylvania 2 grains-powdered sugar No Drawing. Application April 4, 1957 1/2 grain-Starch Serial N0. 650,560 7 Part B 2 Claims. (Cl. 167-82) 3 grainsquinidine gluconate 4 2 A grains-hydrogenated castor oil A grain-starch The part A is thoroughly intermixed in dry, form whereupon the mixture is wet with a solution of 75% isopropyl alcohol and 25% water. The resulting damp mass is then placed upon flat trays and allowed to dry, using warm air. After the mass is dry, the dried mixture is forced through a 12 mesh screen.

The part B is mixed with sufficient isopropyl alcohol In accordance with this invention, the quinidine gluwgtil damp, P Q P mixture 15 heated Y conate is continuously released from the tablet over a 1 fionstan't stlmmg untll Y Q f Castor 011 l i d f i comparable i h h total period f is melted and a homogeneous mixture is obtained. After the bodys digestive processes. Since quinidine gluconate is utilized to insure regularity of heartbeat, it is important that the rate at which this drug is introduced by digestion does not exceed, even temporarily, a level pro- My invention relates to a sustained medication tablet 15 and more particularly relates to a therapeutic compo-, sition of quinidine gluconate for oral administration wherein the tablet will disintegrate at a controlled rate throughout the entire digestive tract releasing the active drug over an extended period of time.

This is a continuation in part of myprior application, Serial No. 399,599, filed December 21, 1953.

.to dry, it is forced through a 12 mesh screen.

The resulting granules of each the part A and part B the drug in excessive quantities, toxicity or other undesirable side effects, are avoided because of the limitation of the maximum amount of the drug at any time available for absorption by the body. Therefore, it becomes practical to accurately control body levels by oral ad- 3 ministration of a single large dos-age of the drug to provide a level suflicient to meet the needs of the heart.

Accordingly, it is an object of my invention to provide a tablet for the oral administration of quinidine gluconate so that the heart will receive the beneficial 40 effects thereof over an extended period of time.

Another object of my invention is to provide a tablet for the oral administration of quinidine gluconate wherein a portion of the active drug is partially released immediately within the mouth followed by constant and controlled release throughout the entire gastro-intestinal tract.

Another object of my invention is to provide a single dosage tablet of quinidine gluconate wherein the therapeutic effectiveness of the drug will be available for distribution to and absorption by the body over a period of from ten to twelve hours.

Another object of my invention is to provide a single dosage tablet of quinidine gluconate wherein release of excessive quantities of this drug at any time within the body is avoided and wherein the amount of this agent available for absorption does not exceed, even temm comeunonal tablet machme' It is to be observed that either of the examples set 23x2 level Producmg toxic or other undeslrable forth above may be varied as to the final tablet size or with departures in the formulation.

60 It is also to be understood that various enteric materials such as waxes, fats, fatty acids and hydrogenated oils may be substituted in suitable proportions for the castor oil in the examples given without departing from the scope of this invention as follows:

machine.

EXAMPLE 2 I This example represents a 10 grain tablet containing 4.5 grains of quinidine gluconate and is a single part mixture as follows:

4.5 grains-quinidine gluconate 3.5 grains-hydrogenated castor oil 1 grain-starch l grainethyl cellulose The hydrogenated castor oil and ethyl cellulose are heated togetheruntil thoroughly melted and homogeneously intermixed. The quinidine glucon-ate is mixed with the starch and enough isopropyl alcohol added until this mixture is damp. The latter mixture is added to the melted liquid of hydrogenated castor oil and ethyl cellulose and while the melt is continuously being heated, the liquid is continuously stirred until a homogeneous mixture is obtained. This mixture is then poured upon trays and allowed to cool and solidify. The solidified material is then granulated by forcing it through a screen or sieve of 12 mesh.

A trace of lubricant such as magnesium stearate is added to the granulations and thoroughly intermixed.

The granules are then compressed into 10 grain tablets Another object of my invention is to provide a single dosage tablet of quinidine gluconate wherein the active drug will be continuously and constantly released at a controlled rate within the body and dispersed throughout the gastro-intestinal tract without becoming stuck en route.

Other objects of my invention are to provide an im- Waxes: proved therapeutic composition of the character de- Bees scribed, that is easily and economically produced and Opal which is highly efiective in operation. Bayberry Referring now to specific embodiments of my inven- Candelilla tion, I show the following examples which are illustra- Carnauba tive of dosage unit forms and their preparation thereof. Ceresin the part B mixture has been placed on trays-and allowed formulations are thoroughly intermixed and a trace of ducing toxic effects. Thus, by preventing the release of 30 magnesium Stearate intermixed rmi are then compressed to 10 gram tablets in a conventional 3 Japan Montan Met-r crystalline-cerilene Paraffin Ozokerite Ouricury Spermaceti Fatty acids:

Oleic acid Tallow fatty acid Stearic acid Cottonseed fatty acid Soyabean fatty acid Cocoanut fatty acid Hydrogenated oils:

Castor Cottonseed Peanut Soyabean Tallow Sperm Corn Olive Palm Rapeseed Cocoanut a period of twelve hours when a single dosage of 1 gram. is taken internally. It has been further foundthat effective quinidine levels can be obtained by the taking by oral administrationof one tablet every hours.

Although my invention has been described in considerable detail, such description is intended as being illustrative rather than limiting, since the invention may be variously embodied, and the scope of the invention is to be determined as claimed.

I claim as my invention:

1. A process of making a therapeutic tablet cont-aim ing quinidine lgluconate suitable for oral administration to control heart action which process consists ,of mixing and heating three and one-half parts by weight of hydrogenated castor oil and one part by weight of ethyl tinuing the stirring and heating until the hydrogenated castor oil, ethyl cellulose, quinidine gluconate and starch become intermixed and form a homogeneous mixture,"

pouring the mixture upon trays and permitting it to cool and solidify, granulating the solidified material by forcing it through a 12 mesh screen, adding a trace of magnesium stearate to the granules and thoroughly intermixing the magnesium stearate with the granules and thereafter compressing the thus obtained mixture into tablets of the desired size.

2. An orally administered therapeutic tablet for use in regulating heart action consisting essentially of four and one-half parts of quinidine gluconate, three and one-half parts of hydrogenated castor oil, one part of starch, one part of ethyl cellulose all parts being by weight and a trace of magnesium stearate homogeneous- 1y mixed together.

OTHER REFERENCES Silver et al.: Manuf. of Compressed Tablets, F. 1.

Stokes Machine Co., 1944, pp. 10, 14, 20 and 21.

Merck Index, 6th ed Merck and Co., Inc., Rahway, N. J., 1952, pp. 817, 818. 

1. A PROCESS OF MAKING A THERAPEUTIC TABLET CONTAIN ING QUINIDINE GLUCONATE SUITABLE FOR ORAL ADMINISTRATION TO CONTROL HEART ACTION WHICH PROCESS CONSISTS OF MIXING ANMD HEATING THREE AND ONE-HALF PARTS BNY WEIGHT OF HYDROGENATED CASTOR OIL AND ONE PART BY WEIGHT OF ETHYL CELLULOSE UNTIL BOTH ARE THOROUGHLY MELTED AND A HOMOGENEOUS MIXTURE OS FORMED, SEPARATELY MIXING FOUR AND ONE-HALF PARTS OF QUINIDINE GLUCONATE BY WEIGHT WITH ONE PART OF STARCH BY WEIGHT AND ONLY A SUFFICIENT AMOUNT OF ISOPROPYL ALCOHOL TO RENDER THE MIXTURE DAMP, ADDING THE DAMP MIXTURE TO THE MOLTEN MIXTURE WHILE HEATING THE MOLTEN MIXTURE, STIRRING TWO MIXTURES AND CONTINUING THE STIRRING AND HEATING UNTIL THE HYDROGENATED CASTOR OIL, ETHYL CELLULOSE, QUINIDINE GLUCONATE AND STARCH BECOME INTERMIXED AND FORM A HOMOGENEOUS MIXTURE, POURING THE MIXTURE UPON TRAYS AND PERMITTING IT TO COOL AND SOLIDIFY, GRANULATING THE SOLIDIFIED MATERIAL BY FORCING IT THROUGH A 12 MESH SCREEN, ADDING A TRACE OF MAGNESIUM STEARATE TO THE GRANULES AND THROUGHLY INTERMIXING THE MAGNESIUM STEARATE WITH THE GRANULES AND THEREAFTER COMPRESSING THE THUS OBTAINED MIXTURE INTO TABLETSS OF THE DESIRED SIZE. 